Method and Apparatus Including Use of Metalloporphyrins for Subsequent Optimization of Radiosurgery and Radiotherapy

ABSTRACT

An apparatus and method for subsequent optimization of radiosurgery and radiotherapy is provided. The invention includes administering a metalloporphyrin to the patient, and then creating a 3-dimensional mapping of tissue through use of PET or SPECT. Malignant and pre-malignant tissue has an affinity for the metalloporphyrin. During treatment, real-time images are also provided which are compared to the previous 3-dimensional mapping. Creation of the real-time images is also achieved through PET or SPECT wherein a metalloporphyrin is administered to the patient. Total administration of radiation is calculated by summing radiation from the inetalloporphyrins and from the radiosurgery/radiotherapy. The amount of radiation delivered by the metalloporphyrins and by the radiosurgery/radiotherapy are adjustable based on a patient&#39;s response to the dual delivery.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of co-application Ser. No.10/176,558, filed on Jun. 21, 2002, entitled “METHOD OF CANCER SCREENINGPRIMARILY UTILIZING NON-INVASIVE CELL COLLECTION, FLUORESCENCE DETECTIONTECHNIQUES, AND RADIO TRACING DETECTION TECHNIQUES”, the disclosure ofwhich is hereby incorporated by reference herein.

FIELD OF THE INVENTION

This invention relates to cancer screening and cancer treatment, andmore particularly, to the use of metalloporphyrins for subsequentoptimization of radiosurgery and/or radiotherapy.

BACKGROUND OF THE INVENTION

There are a number of prior art methods and apparatuses which are usedin the detection and treatment of cancer. Fluorescent markers have beenused to help identify cancerous tissue within a patient. Radio tracersor markers have also been used in the detection and treatment of cancer.

U.S. Pat. No. 5,391,547 discloses a method of using porphyrins to detectlung cancer, and more particularly, to the use of tetra-aryl porphyrins.The porphyrins are used as a fluorescent tracer for cancers of the lung.The porphyrins may be complexed with Copper 64 (⁶⁴Cu) or Copper 67(⁶⁷Cu). Thus, the complex can be used as radio tracers as well. The ⁶⁷Cuprovides a source of beta radiation for selective destruction of lungmalignancies as well as gamma radiation useful for image analysis, as bysingle photon emission computer tomography. The ⁶⁴Cu may be used forradio tracing wherein a positron emission tomography technique can beused to locate the malignant tissue.

U.S. Pat. No. 5,087,636 to Jamieson, et al. discloses a method toidentify and destroy malignant cells in mononuclear cell populations.This method includes the steps of contacting a composition of bonemarrow cells or other cells with a green porphyrin of a specificcompound, irradiating the cell composition with light at a wave lengtheffective to excite fluorescence of the green porphyrin, and thendetecting the presence or absence of fluorescence indicating malignancy.This reference also discloses the steps by which the bone marrow cellsare removed, separated, washed and diluted to an appropriateconcentration for treatment, incubated, centrifuged, and exposed to theirradiating light.

U.S. Pat. Nos. 5,308,608 and 5,149,708 to Dolphin, et al. disclosespecific types of porphyrin compounds which may be used for detection,photosensitization, or the destruction of a targeted biological materialwhen the targeted tissue is contacted with the specified porphyrin, andirradiated with light that excites the compound.

U.S. Pat. No. 5,211,938 to Kennedy, et al. discloses a method ofdetection of malignant and non-malignant lesions by photo chemotherapyof protoporphyrin IX precursors. 5-amino levulinic acid (5-ALA) isadministered to the patient in an amount sufficient to induce synthesisof protoporphyrin IX in the lesions, followed by exposure of the treatedlesion to a photo activating light in the range of 350-640 nanometers.Naturally-occurring protoporphyrin IX is activatable by light which isin the incident red light range (600-700 nanometers) which more easilypasses through human tissue as compared to light of other wave lengthswhich must be used with other types of porphyrins. In short, the use of5-ALA makes cell fluorescence easier to observe, and also greatlyreduces the danger of accidental phototoxic skin reactions in the daysfollowing treatment since protoporphyrin IX precursors have a muchshorter half life in normal tissues than other popularly usedporphyrins.

Present methods relating to cancer screening using fluorescencedetection systems require the use of interventional devices such asendoscopes which have the special capability of delivering specifiedlight frequencies to a targeted tissue of a patient. These endoscopesilluminate the targeted part of the body in which cancer is suspected.The light delivered at a specified frequency illuminates an area whichhas previously been subjected to some type of fluorescent marker, suchas a porphyrin which causes malignant cells to illuminate or fluoresceunder observation of light at the specified frequency. In all cases,introduction of an endoscope into the body requires some type ofsedation or general or local anesthesia. Once a tumor has been locatedby use of the interventional device, depending upon the type of tumor,photo chemotherapy or other treatment means can be used. However, priorto actual treatment, there must be a confirmed test of cancer.Accordingly, the tumor still needs to be sampled by an appropriatebiopsy method. Generally, biopsy methods also require some type ofsedation or anesthesia. Thus, traditional methods of confirming amalignancy may require at least two interventional surgical procedures.

In all uses of photodynamic therapy, it is well known that there arelimitations in such therapy because of the poor penetration of thevisible light required to activate the administered porophyrin so as torender it toxic to the targeted tissue. Particularly for tumors whichare found deep within the body of a patient, repeated interventionalprocedures to treat the neoplastic tissue become infeasible.Accordingly, many types of diseased tissue cannot be effectively treatedthrough photodynamic therapy.

Stereotaxic radio surgery is a well known procedure to treat tumoroustissue. This type of radio surgery is particularly well known fortreating brain tumors. Advances in technology for delivering acollimated surgical ionizing beam now allows medical personnel to treatpatients with cancerous tissue throughout the body.

One company that provides a stereotaxic radio surgery system is Accurayof Boulder, Colo. One system developed by Accuray includes theCyberknife™ system that incorporates a linear accelerator mounted on arobotic arm thereby providing a surgeon with great flexibility indelivering a collimated beam to a targeted area. The Cyberknife has beenused to radiosurgically treat many tumors and other malformations atbody sites which are unreachable by other stereotaxic systems.

Accuracy is the owner of two U.S. patents which claim devices andmethods of carrying out stereotaxic radio surgery and radio therapy.U.S. Pat. No. 5,207,223 discloses a method and apparatus for selectivelyirradiating a target within a patient. A 3-dimensional mapping isprovided of a region surrounding the target. A beaming apparatus emits acollimated beam. Diagnostic beams at a known non-zero angle to oneanother pass through the mapping region. Images of projections areproduced within the mapping region. Electronic representations of theimages are compared with reference data from the 3-dimensional mappingthereby locating the target. The relative positions of the beamingapparatus and the living organism are adjusted in such a manner that thecollimated beam is focused on the target region despite any movement bythe patient during treatment. A comparison is repeated at small timeintervals and, when the comparison so indicates, adjustment is repeated,as needed, and in such a manner that the collimated beam remains focusedon the target region.

U.S. Pat. No. 5,427,097 owned by Accuracy discloses another apparatusand method of performing stereotaxic surgery. A robotic arm and beamgenerating arrangement are provided along a predetermined, non-circularand non-linear path transverse to a collimated beam path, while at thesame time, the collimated beam path is directed into the target region.Thus, the radiosurgical/radiotheraputic beam can be directed through thetarget region from particular treatment points along the transverse pathso as to define a non-spherical target region, thereby allowingtreatment of irregularly shaped tumors or malformations.

One important objective of the inventions disclosed in these referencesowed by Accuracy is to improve the ability to deliver a radiologicalbeam which can be precisely targeted for irradiating targeted tissue,yet limiting exposure of healthy tissue. With the inventions disclosedin the two references, it is possible to perform multiple fractionradiological treatment thereby improving the ability to target andlocalize cancerous or malformed tissue.

While the two references discussed immediately above represent advancesin stereotaxic radiosurgery and radiotherapy, these systems can befurther enhanced by improving the ability to not only map targetedtissue, but also to image the tissue during the radio surgery/radiotherapy procedure thereby ensuring that the radiological beam isprecisely aligned with the targeted tissue. In the above references,3-dimensional mapping is obtained by a CAT scan (CT) or by magneticresonance imaging (MRI). As is well known, computerized tomographyoperates through measurement of the differential absorption of x-raybeams, and the resulting images are in the form of data which ismathematically manipulated through Fourier transform. MRI utilizesnuclear magnetic resonance properties of tissue to obtain 3-dimensionalmapping. CT scanners and MRI scanners are available commercially, andthe data obtained by the scanning can be placed in a digitized formatwhereby it can be stored and manipulated through software in a computer.Although an MRI or CT scan may be adequate under many circumstances, thedisadvantages of CT scanning or MRI scanning is that these types ofscans image the physical structure of tissue, and do not provideinformation regarding the body's chemistry, or cell function.

More recent imaging technologies include positron emission tomography(PET). A PET scan differs from the CT or MRI scan in that the PET scananalyzes cell function, which in many instances provides a better methodby which to determine whether tissue is cancerous. PET typicallyinvolves the administration of a radioactive form of glucose, and thenthe PET scanner tracks and records signals which are emitted by theadministered compound. Actively growing cancer cells typically have muchhigher metabolic rates than normal cells; therefore, the radioactiveglucose is metabolized more quickly by these cancerous tissues, therebycreating distinct signals which can be recorded by the PET scanner. Acomputer then reconstructs the recorded signals into 3-dimensionaldigital images that show areas throughout the body where diseases arepresent. In addition to PET, a related imaging technology includessingle photon emission computer tomography (SPECT) which is also acomputerized imaging technique that produces 3-dimensional images oftissue function. As with PET scanning, a small amount of a radioactiveisotope is administered to a patient, and any increased metabolicactivity present at various body locations can be identified andreviewed to determine whether a patient has diseased or canceroustissue.

One class of chemicals useful for the treatment of tumors is theporphyrins and particularly hematoporphyrin derivatives. These chemicalshave been studied as a result of their selective localization and uptakeinto tumors and malignant tissue and their sensitization of tumortissues to photoirradiation. It has also been suggested that thesechemicals could function as delivery vehicles to target other anticancercompounds to tumor tissues due to their selective uptake into tumortissues. For example, porphyrin molecules may chelate one of manydifferent metal atoms which are then localized to tumor tissues. Thesemetal atoms can be radioactive isotopes which then irradiate thesurrounding tumor tissue after localization to the tumor within ametalloporphyrin. Additionally, the radioactivity emitted can be used inPET or SPECT scanning to create an image of the tumor tissue. However,even without a radioactive component, the metalloporphyrins are stilleffective in selectively delivering a metal atom to tumor tissues. Themetal can then act as a contrast agent to enhance magnetic resonanceimaging or nuclear magnetic resonance imaging. Because the localizationof the metalloporphyrins is based on the chemical properties of theporphyrins themselves and their interaction with characteristics oftumor cells including large interstitial space, high capillarypermeability and lack of lymphatic drainage, and not on differences inmetabolic activities in tissues, they are more selectively taken up andretained by malignant cells than are radioactive glucose molecules. Forthis reason, the metalloporphyrins are also better contrast agents foruse with the different tumor imaging techniques than are radioactiveglucose molecules.

One reference that discloses the use of metalloporphyrins as imageabletumor targeting agents for radiation therapy is U.S. Pat. No. 6,566,517.This reference specifically discloses halogenated derivatives ofboronated porphyrins containing multiple carborane cages whichselectively accumulate in neoplastic tissue, and thus can be used incancer therapies including boron neutron capture therapy andphotodynamic therapy. Although this reference generally discusses theuses of metalloporphyrins for radiation therapy, there is no disclosureof particular procedures by which targeted tissue can be mapped, nor isthere disclosure of other methods by which cancer screening or treatmenttherapy can be conducted other than by boron neutron capture orphotodynamic therapy.

SUMMARY OF THE INVENTION

The present invention provides a method and apparatus including use ofmetalloporphyrins for subsequent optimization of radio surgery and radiotherapy.

The present invention may make use of porphyrin compounds complexed withvarious metals such as silver (Ag), aluminum (Al), cadmium (Cd), cobalt(Co), chromium (Cr), copper (Cu), iron (Fe), gadolinium (Gd), indium(In), lutetium (Lu), magnesium (Mg), manganese (Mn), nickel (Ni),palladium (Pd), platinum (Pt), rhodium (Rh), ruthenium (Ru), scandium(Sc), silicon (Si), tin (Sn), titanium oxide (TiO), vanadium oxide (VO),ytterbium (Yb) and zinc (Zn). These complexes are generally categorizedas metalloporphyrins meaning a porphyrin moiety having a chelatedradioactive isotope of a metal atom. These metalloporphyrins are furtherprocessed so that the metal is in the form of a radioactive isotope. Theresulting radioactive metalloporphyrins thereby constituteradiopharmaceuticals that can be intravenously introduced to thepatient. The affinity of neoplastic tissue for porphyrins results inselective uptake of the radioactive metalloporphyrin, thereby effectingtargeted delivery of therapeutic radiopharmaceuticals. For example, inthe instance of elemental copper chelated by the porphyrin, the coppercan be transformed to radioactive ⁶⁷Cu. In this way, introduction of themetalloporphyrin radiopharmacuetical to the patient is an effectivemeans to deliver measured radiation therapy to targeted tissue. Morespecifically, ⁶⁷Cu provides a source of beta radiation for selectivedestruction of neoplastic sites. Additionally, metalloporphyrincomplexes still provide the ability to simultaneously conductfluorescence detection and phototherapy if desired. Also, themetalloporphyrins provide the ability for observation of the targetedareas through PET (for example, through the use of ⁶⁴Cu) or SPECT (forexample, through use the of ⁶⁷Cu).

A selected group of porphyrin compounds complexed with various metalsare specifically contemplated in the present invention because thesemetalloporphyrins are particularly effective in tumor tissue imaging.The synthetic water soluble porphyrins which contain hydrophilic groupsperipheral to the porphyrin ring facilitate oral administration andavoid the use of additional solubilizing agents. Fe (III) and Mn (III)meso-tetra (4-sulfonatophenyl) porphine (TPPS₄) are water solublemetalloporphyrins that show an increased affinity for solid tumor cells.This affinity is higher than would be expected for the metalloporphyrinsas a general class of compounds. Without intending to be bound by anyone theory, it is believed that this increased affinity for solid tumorsresults from the large size of these metalloporphyrins favoring theirretention in the high capacity interstitial space of tumors. Additionalfactors believed to influence the selective accumulation of themetalloporphyrins in tumors includes charge on the peripheralsubstituents on the porphyrin ring at physiological pH as well as theplasma binding characteristics of the specific metalloporphyrin.Additionally, Fe (III) and Mn (III) TPPS₄ are very stable compoundsmaking them easier to produce, ship and handle either in theirnon-radioactive form or having radioactive isotopes of iron or manganeseatoms. Iron is known to have seven radioisotopes (⁵²Fe, ⁵³Fe, ⁵⁵Fe,⁵⁹Fe, ⁶⁰Fe, ⁶¹Fe, ⁶²Fe) and manganese is known to have six radioisotopes(⁵¹Mn, ⁵²Mn, ⁵³Mn, ⁵⁴Mn, ⁵⁵Mn, ⁵⁶Mn, ⁵⁷Mn) providing many radioisotopesthat can be used in the TPPS₄ prophyrin molecule. Each of these isotopescan be selected for the desired characteristics in terms of half lifeand emission spectra that make for the best use in producing, shippingand using the radioisotope in the scanning procedure. For example, ⁵⁹Fehas a half life about 44.5 days while ⁶²Fe has a half life of about 68seconds. Similarly, ⁵⁴Mn has a half life of 312 days whereas ⁵⁷Mn has ahalf life of about 1.5 minutes. Thus, the desired radioisotope of thesetwo metal atoms can be selected depending on the photon emissioncharacteristics and a suitable or desired half-life. Table I contains alist of the radioisotopes of these two metal atoms and their half-lives.Therefore, the Fe (III) and Mn (III) derivatives of TPPS₄ having aradiometal capable of photo emission are preferred metalloporphyrins foruse in the radiosurgery imaging techniques of the present invention.TABLE I Radioisotope Half-life ⁵²Fe 8.28 hours ⁵³Fe 8.51 minutes ⁵⁵Fe2.73 years ⁵⁹Fe 44.51 days ⁶⁰Fe 1.5 million years ⁶¹Fe 6 minutes ⁶²Fe 68seconds ⁵¹Mn 46.2 minutes ⁵²Mn 5.59 days ⁵³Mn 3.7 million years ⁵⁴Mn312.2 days ⁵⁶Mn 2.58 hours ⁵⁷Mn 1.45 minutes

In accordance with the present invention, the desired metalloporphyrinmay be administered directly to the patient orally, topically, orintravenously. Depending upon the compound introduced, a particularwaiting period is necessary for uptake of the porphyrin compound. Aftersufficient time has been provided for a reaction between the compoundand the targeted cells, a cancer screening procedure may take placewherein the patient is subject to an initial PET or SPECT procedure, andeither a particular location may be imaged, or the entire body may beimaged, for example, to determine the extent to which a tumor hasmetastasized. After conducting the initial imaging procedure,3-dimensional images of targeted body locations are created throughmapping and the images are stored in a computer.

Based upon the results of the initial scanning procedure, subsequentradiosurgery/radiotherapy may take place. In the preferred embodiment,the particular stereotaxic radiosurgery procedure that is contemplatedis the same as that disclosed in the above-mentioned U.S. Pat. Nos.5,207,223 and 5,427,097, these references being incorporated herein byreference in their entireties. The present invention differs from theprocedures disclosed in these prior art references by the method inwhich tissue is imaged. Instead of a CAT scan or MRI scan, 3-dimensionalmapping is achieved by PET or SPECT scanning.

After mapping has been achieved, a beaming apparatus is provided togenerate a collimated surgical ionizing beam of a sufficient strength tocause a targeted region to become necrotic. A preferred beamingapparatus includes an x-ray linear accelerator, although other ionizingradiation sources can be used. Means are provided which allow thecollimated beam to be precisely aligned with the targeted area through acomparison of imaging data which takes place in real-time duringtreatment and the previously mapped images. The imaging which takesplace during the treatment according to the present invention alsoincludes imaging achieved by PET or SPECT. Assuming the time betweencreating the mapping images and treatment by use of the ionizing beamextends beyond the effective half-life of the metalloporphyrin, ametalloporphyrin is again administered to the patient prior to thetreatment, and the metalloporphyrin metabolized in neoplastic tissueallows a very distinct target by which the collimated beam can bealigned. Images which are obtained real-time during treatment arecompared with the previous mapped images, and the collimated beam isadjusted as necessary to maintain the collimated beam in alignment withits targeted location.

By the use of a metalloporphyrin administered to the patient, additionaloptions are provided in treating cancerous or suspect tissue throughradiation therapy/radiosurgical procedures. The metalloporphyrin can bespecifically formulated to provide a desired amount of radiation whichwill not only allow 3-dimensional mapping during a PET/SPECT scanning,but may also provide radiation for treatment by exposure of the suspecttissue during the time in which the metalloporphyrin is metabolized bythe tissue. The later radiosurgical procedure by use of an irradiatingbeam can be dosed to provide the amount of radiation necessary toprovide the additional treatment necessary. Accordingly, the initialexposure of the tissue to the metalloporphyrin may result in desiredtreatment to a specific level, and the remaining required treatment canthen be provided by the irradiating beam. Accordingly, the presentinvention has great flexibility in delivering radiation in two separateways, namely, the administration of the metalloporphyrin and the use ofan irradiating beam. If two administrations of a metalloporphyrin arerequired (i.e., once for mapping and once for providing real-timeimages), then the administrations are collectively dosed to deliver thedesired amount of radiation.

One clear advantage to the above method is that in many instances,administration of the metalloporphyrin will greatly shrink a tumor size;therefore, the beam of radiation can be better focused onto a specifictargeted area thereby further eliminating exposure of healthy tissue tothe irradiating beam.

Thus, with the present invention, radiosurgery/radiotherapy can beoptimized in a manner which enhances the ability to provide aradiosurgical beam to targeted areas in the body and to limit theadverse effects of radiation exposure of healthy tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram illustrating the major components enablingcompletion of the method of the present invention.

DETAILED DESCRIPTION

In order to execute the method and apparatus of the present invention, asystem is provided for delivering a collimated ionizing beam ofradiation to a targeted area of tissue. Examples of such systems tosupport the present invention are disclosed in the U.S. Pat. Nos.5,427,097 and 5,207,223.

Referring to FIG. 1, a representative system to achieve the presentinvention includes a computer 10 with data storage capability that iscapable of executing instructions from software loaded within thecomputer. The computer can store and manipulate 3-dimensional mappingdata images 12 of a patient being treated. The 3-dimensional mapping istypically stored in digital form, and is loaded in the computer 10 forlater comparison purposes. As mentioned above, the 3-dimensional mappingis preferably achieved by SPECT or PET scanning following administrationof a metaloporphyrin to a patient. A beaming apparatus 16 is providedwhich, when activated, emits a collimated surgical ionizing beam of asufficient strength to cause a targeted region to become necrotic. Meansare provided for generating real-time images 14 of tissue at and aroundthe area which is being treated by the collimated beam during thestereotaxic radiosurgery/radiotherapy. In one form, the real-time imagesmay be created by passing first and second diagnostic beams through themapping region, the beams being laterally extensive to provideprojections of the mapping region such as disclosed in the U.S. Pat. No.5,207,223. However, the preferred manner in which to provide real-timeimages for comparison of the previous 3-dimensional mapping is toconduct an additional PET or SPECT procedure. These images 14 in digitalform are then loaded into the computer 10, and software in the computerthen compares the previous 3-dimensional mapping to the real-time imagesto determine the extent to which the collimated beam must be shifted oradjusted to irradiate the desired tissue. In response to comparison ofthe real-time images to the previous 3-dimensional mapping, means areprovided for adjusting the relative position of the beaming apparatus 16thereby adjusting the collimated beam to irradiate the desired target.As disclosed in the U.S. Pat. No. 5,427,09, one means to provideadjustment is through a robotic arm which precisely adjusts thecollimated beam.

Because images which are taken by the PET or SPECT procedures are ofsuch high quality and very accurately image tissue in three dimensions,the collimated beam can be better controlled, and the strength andduration of the beam can be minimized to provide only the amount ofradiation necessary to treat targeted tissue, thereby minimizingexposure of healthy tissue to the radiation.

If it is desired to perform multiple fraction stereotaxic radiation,such treatment can be provided without having to use fiducials or othermarkers since the metalloporphyrins will efficiently localize incancerous tissue, and the images are of such high quality thatapparatuses such as a fiducials are therefore unnecessary to providereference points to help locate suspect areas.

Radiation therapy can be delivered to a patient in the present method inmultiple ways. The initial administration of the metalloporphyrin mayhave significant therapeutic results, and stereotaxic radiation can thencomplete the necessary radiation treatment. The dosages of radiationprovided both by the metalloporphyrin and the irradiating beam can beselectively adjusted to provide the desired level of treatment. In anycase, use of the irradiating beam to treat suspect tissue can be betterdelivered to the patient because PET/SPECT precisely images suspecttissue. Thus, the irradiating beam can thereby be better aligned andminimized in strength and duration to irradiate only the target regionthereby minimizing exposure of healthy tissue that surrounds the suspecttissue.

While the present invention has been described in connection with aspecific preferred embodiment, it shall be understood that variousmodifications to the present invention can be made within the spirit andthe scope of the present invention as defined by the appended claims.

1-7. (canceled)
 8. An apparatus for carrying out radiosurgery byselectively irradiating a targeted area of tissue within a patient, andby providing a selected dose of radiation through administration of anirradiating compound in conjunction with the radiosurgery, comprising: acomputer including data storage memory having stored therein a3-dimensional mapping of at least a portion of the patient, the mappingcovering a mapping region that is larger than a target region; a beamingapparatus adapted to emit a radiosurgical beam of radiation sufficientto cause the target region to become necrotic; means for providingdigital electronic images of the target region during activation of saidradiosurgical beam, said means for providing including PET or SPECTwhich produces said images based on a metalloporphyrin previouslyadministered to the patient; means for comparing the 3-dimensionalmapping with real-time images taken during activation of saidradiosurgical beam; and means for adjusting the relative position of thebeaming apparatus and the patient as needed due to any movement of thetarget region relative to the radiosurgical beam in response to thecomparison of the 3-dimensional mapping and image data taken duringactivation thereby ensuring that the radiosurgical beam is continuouslyfocused onto the target region.
 9. An apparatus as claimed in claim 8,wherein: the 3-dimensional mapping is achieved by PET or SPECT scanning.10. An apparatus as claimed in claim 8, wherein: said irradiatingcompound administered to the patient is meso-tetra (4-sulfonatophenyl)porphine complexed with a radiometal imageable by SPECT or PET imagingselected from the group consisting of manganese and iron.
 11. Anapparatus for carrying out radiosurgery by selectively irradiating atargeted area of tissue within a patient, and by providing a selecteddose of radiation through administration of an irradiating compound inconjunction with the radiosurgery, comprising: a computer including datastorage memory having stored therein a 3-dimensional mapping of at leasta portion of the patient, the mapping covering a mapping region that islarger than a target region and achieved by PET or SPECT scanning; abeaming apparatus adapted to emit a radiosurgical beam of radiationsufficient to cause the target region to become necrotic; means forproviding digital electronic images of the target region duringactivation of said radiosurgical beam, said means for providingincluding PET or SPECT which produces said images based on aradio-imageable form of Mn (III) meso-tetra (4-sulfonatophenyl) porphinepreviously administered to the patient; means for comparing the3-dimensional mapping with real-time images taken during activation ofsaid radiosurgical beam; and means for adjusting the relative positionof the beaming apparatus and the patient as needed due to any movementof the target region relative to the radiosurgical beam in response tothe comparison of the 3-dimensional mapping and image data taken duringactivation thereby ensuring that the radiosurgical beam is continuouslyfocused onto the target region.